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The excessive lactate in the tumor microenvironment always leads to poor therapeutic outcomes of chemotherapy. In this study, a self-driven bioreactor (defined as SO@MDH, where SO is Shewanella oneidensis MR-1 and MDH is MIL-101 metal-organic framework nanoparticles/doxorubicin/hyaluronic acid) is rationally constructed via the integration of doxorubicin (DOX)-loaded metal-organic framework (MOF) MIL-101 nanoparticles with SO to sensitize chemotherapy. Owing to the intrinsic tumor tropism and electron-driven respiration of SO, the biohybrid SO@MDH could actively target and colonize hypoxic and eutrophic tumor regions and anaerobically metabolize lactate accompanied by the transfer of electrons to Fe 3+ , which is the key component of the MIL-101 nanoparticles. As a result, the intratumoral lactate would undergo continuous catabolism coupled with the reduction of Fe 3+ to Fe 2+ and the subsequent degradation of MIL-101 frameworks, leading to an expeditious drug release for effective chemotherapy. Meanwhile, the generated Fe 2+ will be promptly oxidized by the abundant hydrogen peroxide in the tumor microenvironment to reproduce Fe 3+ , which is, in turn, beneficial to circularly catabolize lactate and boost chemotherapy. More importantly, the consumption of intratumoral lactic acid could significantly inhibit the expression of multidrug resistance-related ABCB1 protein (also named P-glycoprotein (P-gp)) for conquering drug-resistant tumors. SO@MDH demonstrated here holds high tumor specificity and promising chemotherapeutic efficacy for suppressing tumor growth and overcoming multidrug resistance, confirming its potential prospects in cancer therapy.

A tumor cell membrane-camouflaged therapeutic system was fabricated to eliminate tumors by embedding apyrase and glucose oxidase (GOx) into zeolitic imidazolate framework-8 (ZIF-8) nanoparticles for tumor-targeted metabolic therapy. Experimental results demonstrated that these functional nanoparticles could disturb the energy supply of tumor cells by depleting ATP and glucose and efficiently induce tumor cell death.

UiO-68 metal-organic framework nanoparticles (NMOFs) are loaded with a doxorubicin drug (fluorescent dye analogs) and locked by means of structurally engineered duplex nucleic acid structures, where one strand is covalently linked to the NMOFs and the second strand is hybridized with the anchor strand. Besides the complementarity of the second strand to the anchor sequence, it includes the complementary sequence to the microRNAs (miRNA)-21 or miRNA-221 that is specific miRNA biomarker for MCF-7 breast cancer cells or OVCAR-3 ovarian cancer cells. In the presence of the respective miRNA biomarkers, the miRNA-induced displacement of the strand associated with the anchor strand proceeds, resulting in the release of DNA/miRNA duplexes. The released duplexes are, however, engineered to be digested in the presence of exonuclease III, Exo III, a process that recycles the miRNAs and provides the autonomous amplified unlocking of the NMOFs and the release of the doxorubicin load (or the fluorescent dye analogs) even at low concentrations of miRNA. Preliminary cell experiments reveal that the respective NMOFs are unlocked by the miRNA-21 or miRNA-221, resulting in selective cytotoxicity toward MCF-7 breast cancer cells or OVCAR-3 ovarian cancer cells., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Zeolitic Zn 2+ -imidazolate cross-linked framework nanoparticles, ZIF-8 NMOFs, are used as "smart" glucose-responsive carriers for the controlled release of drugs. The ZIF-8 NMOFs are loaded with the respective drug and glucose oxidase (GOx), and the GOx-mediated aerobic oxidation of glucose yields gluconic acid and H 2 O 2 . The acidification of the NMOFs' microenvironment leads to the degradation of the nanoparticles and the release of the loaded drugs. In one sense-and-treat system, GOx and insulin are loaded in the NMOFs. In the presence of glucose, the nanoparticles are unlocked, resulting in the release of insulin. The release of insulin is controlled by the concentration of glucose. In the second sense-and-treat system, the NMOFs are loaded with the antivascular endothelial growth factor aptamer (VEGF aptamer) and GOx. In the presence of glucose, the ZIF-8 NMOFs are degraded, leading to the release of the VEGF aptamer, which acts as a potential inhibitor of the angiogenetic regeneration of blood vessels by VEGF. As calcination of the VEGF-generated blood vessels leads to blindness of diabetic patients, the functional NMOFs might act as "smart" materials for the treatment of macular diseases. The potential cytotoxicity of the NMOFs originated from the GOx-generated H 2 O 2 is resolved by the co-immobilization of the H 2 O 2 -scavanger catalase in the NMOFs.